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18 papers found.
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Golgin45-Syntaxin5 Interaction Contributes to Structural Integrity of the Golgi Stack

The unique stacked morphology of the Golgi apparatus had been a topic of intense investigation among the cell biologists over the years. We had previously shown that the two Golgin tethers (GM130 and Golgin45) could, to a large degree, functionally substitute for GRASP-type Golgi stacking proteins to sustain normal Golgi morphology and function in GRASP65/55-double depleted HeLa...

Repeat domain-associated O-glycans govern PMEL fibrillar sheet architecture

PMEL is a pigment cell-specific protein that forms a functional amyloid matrix in melanosomes. The matrix consists of well-separated fibrillar sheets on which the pigment melanin is deposited. Using electron tomography, we demonstrate that this sheet architecture is governed by the PMEL repeat (RPT) domain, which associates with the amyloid as an accessory proteolytic fragment...

Reducing protein regulator of cytokinesis 1 as a prospective therapy for hepatocellular carcinoma

Proteins that bind to microtubule are important for cell cycle, and some of these proteins show oncogenic characteristics with mechanisms not fully understood. Herein we demonstrate overexpression of protein regulator of cytokinesis 1 (PRC1), a microtubule-associated regulator of mitosis, in human hepatocellular carcinoma (HCC). Moreover, upregulated PRC1 is associated with lower...

Melanosomal formation of PMEL core amyloid is driven by aromatic residues

journals • PubMed • Google ScholarSearch for Xinran Liu in:Nature Research journals • PubMed • Google ScholarSearch for Ralf M. Leonhardt in:Nature Research journals • PubMed • Google Scholar Contributions

ANGPTL8 negatively regulates NF-κB activation by facilitating selective autophagic degradation of IKKγ

Excessive nuclear factor-κB (NF-κB) activation mediated by tumor necrosis factor α (TNFα) plays a critical role in inflammation. Here we demonstrate that angiopoietin-like 8 (ANGPTL8) functions as a negative feedback regulator in TNFα-triggered NF-κB activation intracellularly. Inflammatory stimuli induce ANGPTL8 expression, and knockdown or knockout of ANGPTL8 potentiates TNF...

Synaptotagmin-1 and -7 Are Redundantly Essential for Maintaining the Capacity of the Readily-Releasable Pool of Synaptic Vesicles

In forebrain neurons, Ca2+ triggers exocytosis of readily releasable vesicles by binding to synaptotagmin-1 and -7, thereby inducing fast and slow vesicle exocytosis, respectively. Loss-of-function of synaptotagmin-1 or -7 selectively impairs the fast and slow phase of release, respectively, but does not change the size of the readily-releasable pool (RRP) of vesicles as measured...

APP Is Cleaved by Bace1 in Pre-Synaptic Vesicles and Establishes a Pre-Synaptic Interactome, via Its Intracellular Domain, with Molecular Complexes that Regulate Pre-Synaptic Vesicles Functions

Amyloid Precursor Protein (APP) is a type I membrane protein that undergoes extensive processing by secretases, including BACE1. Although mutations in APP and genes that regulate processing of APP, such as PSENs and BRI2/ITM2B, cause dementias, the normal function of APP in synaptic transmission, synaptic plasticity and memory formation is poorly understood. To grasp the...

Identifying Vulnerable Nodes of Complex Networks in Cascading Failures Induced by Node-Based Attacks

In the research on network security, distinguishing the vulnerable components of networks is very important for protecting infrastructures systems. Here, we probe how to identify the vulnerable nodes of complex networks in cascading failures, which was ignored before. Concerned with random attack (RA) and highest load attack (HL) on nodes, we model cascading dynamics of complex...

Identifying Vulnerable Nodes of Complex Networks in Cascading Failures Induced by Node-Based Attacks

In the research on network security, distinguishing the vulnerable components of networks is very important for protecting infrastructures systems. Here, we probe how to identify the vulnerable nodes of complex networks in cascading failures, which was ignored before. Concerned with random attack (RA) and highest load attack (HL) on nodes, we model cascading dynamics of complex...

Central Presynaptic Terminals Are Enriched in ATP but the Majority Lack Mitochondria

Synaptic neurotransmission is known to be an energy demanding process. At the presynapse, ATP is required for loading neurotransmitters into synaptic vesicles, for priming synaptic vesicles before release, and as a substrate for various kinases and ATPases. Although it is assumed that presynaptic sites usually harbor local mitochondria, which may serve as energy powerhouse to...

Cascading Dynamics of Heterogenous Scale-Free Networks with Recovery Mechanism

In network security, how to use efficient response methods against cascading failures of complex networks is very important. In this paper, concerned with the highest-load attack (HL) and random attack (RA) on one edge, we define five kinds of weighting strategies to assign the external resources for recovering the edges from cascading failures in heterogeneous scale-free (SF...

Cascading Dynamics of Heterogenous Scale-Free Networks with Recovery Mechanism

In network security, how to use efficient response methods against cascading failures of complex networks is very important. In this paper, concerned with the highest-load attack (HL) and random attack (RA) on one edge, we define five kinds of weighting strategies to assign the external resources for recovering the edges from cascading failures in heterogeneous scale-free (SF...

A dynamin 1-, dynamin 3- and clathrin-independent pathway of synaptic vesicle recycling mediated by bulk endocytosis

The exocytosis of synaptic vesicles (SVs) elicited by potent stimulation is rapidly compensated by bulk endocytosis of SV membranes leading to large endocytic vacuoles (‘bulk’ endosomes). Subsequently, these vacuoles disappear in parallel with the reappearance of new SVs. We have used synapses of dynamin 1 and 3 double knock-out neurons, where clathrin-mediated endocytosis (CME...

Neural-Specific Deletion of Htra2 Causes Cerebellar Neurodegeneration and Defective Processing of Mitochondrial OPA1

HTRA2, a serine protease in the intermembrane space, has important functions in mitochondrial stress signaling while its abnormal activity may contribute to the development of Parkinson’s disease. Mice with a missense or null mutation of Htra2 fail to thrive, suffer striatal neuronal loss, and a parkinsonian phenotype that leads to death at 30–40 days of age. While informative...

Characterization of Age-Dependent and Progressive Cortical Neuronal Degeneration in Presenilin Conditional Mutant Mice

Presenilins are the major causative genes of familial Alzheimer's disease (AD). Our previous study has demonstrated essential roles of presenilins in memory and neuronal survival. Here, we explore further how loss of presenilins results in age-related, progressive neurodegeneration in the adult cerebral cortex, where the pathogenesis of AD occurs. To circumvent the requirement of...

The RNA Template Channel of the RNA-Dependent RNA Polymerase as a Target for Development of Antiviral Therapy of Multiple Genera within a Virus Family

The genus Enterovirus of the family Picornaviridae contains many important human pathogens (e.g., poliovirus, coxsackievirus, rhinovirus, and enterovirus 71) for which no antiviral drugs are available. The viral RNA-dependent RNA polymerase is an attractive target for antiviral therapy. Nucleoside-based inhibitors have broad-spectrum activity but often exhibit off-target effects...